OCALIVA

Farnesoid X Receptor (FXR) Agonists

Take obeticholic acid orally with or without food.
For patients taking a bile acid binding resin, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid binding resin, or at as great an interval as possible.

eczema vaccinatum / Delayed / 3.0-6.0
hepatic encephalopathy / Delayed / 0-1.0
hepatic failure / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
biliary obstruction / Delayed / Incidence not known
hepatic decompensation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known

decreased HDL cholesterol (HDL-C) concentration / Delayed / 9.0-20.0
constipation / Delayed / 7.0-7.0
peripheral edema / Delayed / 3.0-7.0
palpitations / Early / 3.0-7.0
hypothyroidism / Delayed / 0-6.0
ascites / Delayed / 0-1.0
jaundice / Delayed / Incidence not known
cholangitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known

pruritus ani / Early / 0-70.0
ocular pruritus / Rapid / 0-70.0
pruritus / Rapid / 56.0-70.0
asthenia / Delayed / 0-25.0
fatigue / Early / 19.0-25.0
abdominal pain / Early / 10.0-19.0
rash / Early / 7.0-10.0
maculopapular rash / Early / 0-10.0
urticaria / Rapid / 0-10.0
arthralgia / Delayed / 6.0-10.0
syncope / Early / 0-7.0
dizziness / Early / 7.0-7.0
fever / Early / 7.0-7.0
vomiting / Early / Incidence not known
nausea / Early / Incidence not known

Patients who are taking obeticholic acid for primary biliary cirrhosis/cholangitis (PBC) and have hepatic biliary cirrhosis with symptoms of hepatic decompensation such as ascites, jaundice, variceal GI bleeding, hepatic encephalopathy, or certain abnormalities in liver function tests (LFTs) should talk to their health care provider to see if this medication should be stopped. Obeticholic acid is contraindicated in patients with complete biliary obstruction or advanced cirrhosis, defined as cirrhosis with current (e.g., Child-Pugh Class B or C) or prior evidence of hepatic decompensation (e.g., hepatic encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastro- or esophageal varices, persistent thrombocytopenia). In postmarketing reports, hepatotoxicity such as hepatic decompensation and hepatic failure (some cases fatal or resulting in liver transplant), have been reported with obeticholic acid treatment in patients with primary biliary cholangitis (PBC) with cirrhosis, either compensated or decompensated. The median time to hepatic decompensation (e.g., new onset ascites) was 4 months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and liver failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. The FDA identified 25 cases of primary biliary cirrhosis/cholangitis (PBC) patients with cirrhosis (compensated or decompensated) taking obeticholic acid at recommended dosages prior to the initial liver-related adverse event. Eighteen of 25 cases occurred in PBC patients with compensated cirrhosis who experienced liver injury (hepatotoxicity) that led to decompensation; although the disease in these PBC patients was not expected to progress rapidly, they experienced accelerated deterioration in clinical status within months of starting obeticholic acid. Four PBC patients with compensated cirrhosis required a liver transplant within 1.3 years after starting obeticholic acid, and 1 PBC patient with compensated cirrhosis died from liver failure. The other 7 cases occurred in PBC patients with decompensated cirrhosis, 2 of whom died. Although there was a temporal relationship between obeticholic acid initiation and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease. The median time to a new decompensation event (e.g., hepatic encephalopathy) after initiating obeticholic acid was 2.5 months, ranging from 10 days to 8 months. In addition to liver transplant, evidence for liver decompensation included events such as new-onset ascites, variceal GI bleeding, hepatorenal syndrome, and worsening synthetic function. The most common associated liver-related adverse event among the 25 cases was worsening total bilirubin. Hepatotoxicity was observed in the obeticholic acid clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of obeticholic acid of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with obeticholic acid in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for biochemical response, tolerability, disease progression of PBC. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time. Permanently discontinue obeticholic acid in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. Also monitor patients for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine. Permanently discontinue obeticholic acid in patients developing these symptoms. If severe intercurrent illness occurs, interrupt treatment with obeticholic acid and monitor the patient's liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting obeticholic acid treatment.

OCALIVA

Rx

Farnesoid X receptor (FXR) agonist
For primary biliary cholangitis (PBC) in patients without cirrhosis or who have compensated cirrhosis without evidence of portal hypertension; used as monotherapy in adults unable to tolerate ursodeoxycholic acid (UDCA) or in combination with UDCA in adults with inadequate response to UDCA alone
Boxed warning for hepatic decompensation and failure in PBC patients with cirrhosis; contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis and portal hypertension

5 mg PO once daily for the first 3 months. After the first 3 months, for patients who have not achieved an adequate reduction in alkaline phosphatase (ALP) and/or total bilirubin and are tolerating 5 mg/day, increase to a maximum dosage of 10 mg PO once daily.

Treatment with obeticholic acid should be initiated and monitored by a health care provider with experience managing primary biliary cholangitis/primary biliary cirrhosis (PBC). Routinely monitor patients for progression of PBC with laboratory and clinical assessments. Permanently discontinue obeticholic acid in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Interrupt treatment during severe intercurrent illness. Plasma exposure to obeticholic acid and its active conjugates increases significantly in patients with increasing hepatic impairment, whichis associate with an increased risk for adverse hepatic events.
Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is recommended; carefully monitor patients as recommended.
Moderate to severe hepatic impairment (Child-Pugh Class B or C and others): Contraindicated in patients with decompensated cirrhosis (e.g., Child-Pugh Class B or C), in those with a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia).

No dosage adjustment is recommended as there is minimal renal excretion of the drug.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Bendamustine: (Major) Consider the use of an alternative therapy if obeticholic acid treatment is needed in patients receiving bendamustine. Concomitant use of obeticholic acid may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with obeticholic acid is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as caffeine. Concomitant administration of 200 mg caffeine as a single dose with obeticholic acid 10 mg once daily resulted in a 42% increase in caffeine AUC and a 6% increase in caffeine Cmax. Therapeutic monitoring is recommended with coadministration. No specific management is recommended except in patients who complain of caffeine-related side effects like nausea, tremor, or palpitations. In such patients, the dosage of caffeine-containing medications or the ingestion of caffeine-containing products may need to be reduced.
Caffeine; Sodium Benzoate: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Cholestyramine: (Moderate) Bile acid binding resins such as cholestyramine absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of obeticholic acid. If used together, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid resin, or at as great an interval as possible.
Clomipramine: (Moderate) Monitor for an increase in clomipramine-related adverse reactions if concomitant use of obeticholic acid is necessary; a clomipramine dose reduction may be necessary. Concomitant use may increase clomipramine exposure; clomipramine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with obeticholic acid and monitor for adverse reactions. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is a CYP1A2 substrate; obeticholic acid is a weak CYP1A2 inhibitor.
Colesevelam: (Moderate) Bile acid binding resins such as colesevelam absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of obeticholic acid. If used together, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid resin, or at as great an interval as possible.
Colestipol: (Moderate) Bile acid binding resins such as colestipol absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of obeticholic acid. If used together, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid resin, or at as great an interval as possible.
Cyclosporine: (Major) Avoid coadministration of obeticholic acid, an inhibitor of the bile salt efflux pump (BSEP) with other BSEP inhibitors, such as cyclosporine; if coadministration is necessary, monitor serum transaminases and bilirubin. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms.
Ergotamine; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and obeticholic acid is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; obeticholic acid is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Flutamide: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as flutamide. Therapeutic monitoring is recommended with coadministration.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with obeticholic acid is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with obeticholic acid is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with obeticholic acid is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Mexiletine: (Moderate) Monitor for increased toxicity of mexiletine if coadministered with obeticholic acid. Coadministration may increase serum concentrations of mexiletine. Mexiletine is a CYP1A2 substrate and obeticholic acid is a weak CYP1A2 inhibitor.
Pimozide: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with obeticholic acid. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; obeticholic acid is a weak CYP1A2 inhibitor.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if concomitant use of obeticholic acid is necessary. Concomitant use may increase propafenone exposure; propafenone is a CYP1A2 substrate and obeticholic acid is a weak CYP1A2 inhibitor.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and obeticholic acid. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; obeticholic acid is a weak CYP1A2 inhibitor.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations and watch for an increase in theophylline-related adverse reactions if coadministration with obeticholic acid is necessary; a theophylline dose reduction may be necessary. Theophylline is a CYP1A2 substrate with a narrow therapeutic index and obeticholic acid is a CYP1A2 inhibitor. (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as theophylline, aminophylline. Since the therapeutic range is narrow, it is prudent to monitor theophylline serum concentrations upon initiation, dosage adjustment, or discontinuation of medications that may alter the function of CYP1A2.
Tizanidine: (Major) Avoid concomitant use of tizanidine and obeticholic acid as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and obeticholic acid is a weak CYP1A2 inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with obeticholic acid is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The R-enantiomer of warfarin is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance. Concomitant use of 25 mg warfarin as a single dose with obeticholic acid 10 mg once daily resulted in a 13% increase in systemic exposure to S-warfarin and an 11% decrease in maximum INR.

OCALIVA Oral Tab: 5mg, 10mg

10 mg PO once daily.

10 mg PO once daily.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Obeticholic acid is an agonist for FXR, a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulation bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids.
 
In clinical trials, alkaline phosphatase (ALP) reduction was observed to plateau at approximately 3 months in most patients treated with obeticholic acid 5 mg PO daily. Increasing the dose based on tolerability and response provided additional reduction in ALP in the majority of patients. Administration of 10 mg PO daily was associated with a 173% increase in concentrations of FGF-19, and FXR-inducible enterokine involved in bile acid homeostasis, from baseline to month 12. Concentrations of cholic acid and chenodeoxycholic acid were reduced 2.7 micromolar 1.4 micromolar, respectively, from baseline to month 12. The clinical relevance of these findings is unknown.

Obeticholic acid is administered orally. Plasma binding of obeticholic acid and its conjugates is greater than 99%. The volume of distribution of obeticholic acid is 618 L. The volumes of distribution of the conjugates have not been determined.
 
Obeticholic acid is conjugated with glycine or taurine in the liver to glyco-obeticholic acid and tauro-obeticholic acid and secreted into bile. The glycine and taurine conjugates are absorbed in the small intestine leading to enterohepatic recirculation. The conjugated can be deconjugated in the ileum and colon by intestinal microbiota, leading to the conversion to obeticholic acid than can be reabsorbed or excreted in the feces, the principal route of elimination. After daily administration, there is accumulation of the conjugates, which have in vitro pharmacological activities similar to the parent drug. A third metabolite, 3-glucuronide, is formed, but is considered to have minimal pharmacologic activity. About 87% of the obeticholic acid dose is excreted in the feces through biliary secretion. Less than 3% of the dose is excreted in the urine with no detection of obeticholic acid.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2 and BSEP
Obeticholic acid is a weak CYP1A2 inhibitor and may increase exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index is recommended. Down-regulation of mRNA was observed in a concentration-dependent fashion for CYP1A2 and CYP3A4 by obeticholic acid and its conjugates. In vitro studies suggest obeticholic acid can inhibit CYP3A4; however, in vivo studies indicate no inhibition of CYP3A4. Obeticholic acid and its conjugates are not expected to inhibit OATP1B1, OATP1B3, P-glycoprotein (P-gp), BCRP, OAT1, OAT3, OCT2,or MATE transporters. Obeticholic acid is not expected to inhibit CYP enzymes 2B6, 2C8, 2C9, 2C19, or 2D6, nor induce CYP enzymes 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4 at recommended doses. In vitro studies showed that obeticholic acid and its glycine and taurine conjugates inhibit the bile salt efflux pump (BSEP) in a dose dependent manner. However, an in vivo drug interaction due to inhibition of BSEP in patients using the recommended dosage regimen appears unlikely. Induction of BSEP can occur by FXR activation by obeticholic acid and its conjugates, which are FXR agonists.

After multiple doses of obeticholic acid 10 mg PO once daily, peak plasma concentrations (Cmax) occurred at a median time (Tmax) of approximately 1.5 hours. The median Tmax for both glyco- and tauro-conjugates was 10 hours. Coadministration with food did not alter the extent of obeticholic acid absorption.  After multiple doses of 5, 10, and 25 mg PO once daily for 14 days, the systemic exposures of obeticholic acid increased dose proportionally. Exposures to the conjugates and total obeticholic acid (the sum of obeticholic acid and its 2 active conjugates) increase more than proportionally with the dose.

The limited available human data on the use of obeticholic acid during pregnancy are not sufficient to inform a drug-associated risk. In animal studies, no developmental abnormalities or fetal harm was noted.

There is no information on the presence of obeticholic acid in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.